ABSTRACT The goal of this project, entitled ?Validation of a Behavioral Measure of Executive Function as a Resource to Support Preparedness for Clinical Trials in Down Syndrome? is to develop and distribute resources for use by the broader scientific community, intended for furthering research and increasing preparedness for clinical trials in individuals with Down syndrome (DS). With an incidence of 1 in 700 live births in the U.S., DS, caused by trisomy 21, is the most common genetic cause of intellectual disability. In recent years, there has been tremendous progress in basic research that has led to promising clinical trials for Down syndrome. One major obstacle to the demonstration of efficacy in human trials in individuals with DS has been the lack of validated outcome measures to assess improvement in function. To this end, there is a key need for assessment tools that are ecologically valid for assessing key neurobehavioral functions in DS, and in delineating outcomes for behavioral and pharmacological clinical trials. Importantly, these tools need to be time-efficient and feasible for research use in a variety of healthcare settings and assessment platforms, by a wide range of providers. Executive function (EF) describes the range of skills required for purposeful goal-directed activity, socially appropriate conduct, and independent regulation of action and affect. Among individuals with DS, EF deficits are recognized as a key contributor to functional impairment, beyond that attributable to IQ alone. There is converging evidence that the caregiver ratings of EF are more sensitive and more ecologically valid than performance-based tests in identifying EF-dependent life skills, and explaining within-syndrome heterogeneity. The proposed work represents a critical next step for validating and adapting the Behavior Rating Inventory for Executive Function-2 (BRIEF2) in individuals with DS as a research tool that will have immediate utility in clinical trials. The resulting data, to be made available through DS-Connect, will serve as a resource for the research community for new clinical trials and investigations into phenotypic variation in DS. Specifically, the study will develop and distribute a dataset of caregiver ratings of EF in 1000 individuals (ages 8-25 years) with DS, and will deliver the distributions and item-level dataset itself, which will be shared in DS-Connect. The resulting dataset will be the largest to date in individuals with Down syndrome. Examination of reliability (temporal stability), construct utility, and item utility of the BRIEF2 in this sample will allow for provision of a recommended set of items for a short form of the BRIEF2, based on reliability, validity and utility data, to be used for clinical trials in Down syndrome.